3-Caffeoyl, 4-dihydrocaffeoylquinic acid from Salicornia herbacea inhibits tumor cell invasion by regulating protein kinase C-δ-dependent matrix metalloproteinase-9 expression

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Title
3-Caffeoyl, 4-dihydrocaffeoylquinic acid from Salicornia herbacea inhibits tumor cell invasion by regulating protein kinase C-δ-dependent matrix metalloproteinase-9 expression
Author(s)
Y P Hwang; H J Yun; J H Choi; Hyo Kon Chun; Y C Chung; S K Kim; B H Kim; K I Kwon; T C Jeong; K Y Lee; H G Jeong
Bibliographic Citation
Toxicology Letters, vol. 198, no. 2, pp. 200-209
Publication Year
2010
Abstract
In this study, we determined the effects of a novel chlorogenic acid, 3-caffeoyl, 4-dicaffeoylquinic acid (CDCQ) isolated from Salicornia herbacea, on tumor invasion and migration in human fibrosarcoma HT-1080 cells and investigated the possible mechanism(s) involved. CDCQ reduced the phorbol myristate acetate (PMA)-induced activation of matrix metalloproteinase (MMP)-9 and MMP-2 and inhibited cell invasion and migration. CDCQ suppressed PMA-induced expression of MMP-9 mRNA and protein by suppressing the transcription factor AP-1, without changing the level of tissue inhibitor of metalloproteinase (TIMP)-1. CDCQ-inhibited PMA-induced MMP-2 expression by suppressing membrane-type 1 MMP (MT1-MMP), but did not alter the TIMP-2 level. CDCQ also inhibited the PMA-induced nuclear translocation of c-Jun and c-Fos, which are upstream of PMA-induced MMP-9 expression. Furthermore, CDCQ strongly repressed PMA-induced phosphorylation of ERK, p38 MAPK, and JNK, which are dependent on the PKCδ pathway. In conclusion, we demonstrated that the anti-invasive effects of CDCQ occur through the inhibition of AP-1 and signaling pathways involving PKCδ and three MAPKs, leading to the downregulation of MMP-9 expression. Thus, CDCQ is an effective anti-metastatic agent that functions by downregulating MMP-9 gene expression.
Keyword
3-Caffeoyl, 4-dihydrocaffeoylquinic acidAntitumor activityInvasionMMP-9PKCδ
ISSN
0378-4274
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.toxlet.2010.06.018
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > SME Support Center > 1. Journal Articles
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